Our long-term objective is to apply the chemistry of N- substituted porphyrins to the development of specific DNA alkylators and imaging agents for gamma scanning and positron emission tomography (PET). DNA alkylators and especially those which cross link DNA are potent cytotoxic agents and have been useful for cancer therapy. One aim is to link N-alkylporphyrins (which are potent alkylators of high specificity) to known DNA intercalators to localize the alkylating agent in the vicinity of the DNA bases. Diagnostic imaging by gamma or positron emission uses a small dose of radioactive material to determine the position of abnormal tissue, lesions or blockages, avoiding exploratory surgery. For gamma imaging, N-substituted porphyrins have been bound to antibodies and 67Cu has been rapidly and firmly complexed. Thorough purification and characterization and studies of the distribution of radiolabelled porphyrin-monoclonal antibody adducts will be undertaken. Many isotopes are potentially useful for PET scanning. Beginning with studies of 64Cu complexes, the possibility of imaging inflamed lymph nodes, lung-localized antigen and tumor tissue will be investigated by comparisons of biodistribution data and PET scans. The characteristics of metalloporphyrins formed with other metallic isotopes (such as those of cobalt, nickel and indium) will be determined.